Effect of Mosapride on Postoperative Ileus in Patients Undergoing Colorectal Surgery (ILEUS)

• ClinicalTrials.gov Identifier: NCT02056405
• Recruitment Status: Unknown
• First Posted: February 6, 2014
• Last Update Posted: December 17, 2015
• Sponsor: Hospital Italiano de Buenos Aires
• Information provided by (Responsible Party): Diego Hernan Giunta, MD, Hospital Italiano de Buenos Aires

Study Description

Brief Summary:

Postoperative Ileus is defined as the transient postoperative functional inhibition of propulsive bowel activity. The ethiology of this process can best be described as multifactorial. In its pathogenesis different mechanisms are involved such as hormones and neuropeptides, inflammation, narcotics and the Autonomic nervous system. Is one of the most common causes of prolonged hospital stays after abdominal surgery, thereby increasing health-care resource utilization. More importantly, it causes patient discomfort in the form of nausea, vomiting, and stomach cramps. It has a variable duration but is usually solved in 3 to 4 days. Prolonged Ileus is associated with postoperative complications like an increase on urinary and pulmonary infections, profound venous thrombosis and wound-site complications.

Mosapride is a prokinetic agent that acts as a selective serotonin agonist (5- HT4) that facilitates acetylcholine release from the intrinsic plexus. This accelerates gastric emptying and propulsive peristaltic movements on the lower intestines. Mosapride has no action over the central nervous system therefore the lesser side effects like cardiac arrhythmias and extrapyramidal symptoms. For being a safer drug we chose it to be the center of our research.

Two randomized controlled trials studied Mosapride concluding it shortens PI after colorectal surgery. However these trials took place on specific populations (Orientals) with less than 50 patients and only one of them included laparoscopic treatment specifically. Also the end point of these studies didn't consider the impact of PI over hospital stay or costs to the health system.

We therefore decided to conduct a prospective randomized study in patients undergoing laparoscopic colorectal surgery for colon cancer. The patients will be randomized to receive treatment or placebo after surgery. With this study we intend to prove that patients treated with mosapride immediately after surgery suffer from shorter postoperative ileus with earlier oral intake and shorter hospital stay.

The primary aim of the trial is to assess the effectiveness of the use of Mosapride in shortening the duration of the Postoperative ileus in patients undergoing colorectal laparoscopic surgery. The trial hypothesis is that the standardized use of Mosapride immediately after colorectal laparoscopic surgery is safe and accelerates the recovery of propulsive bowel activity, thereby shortening postoperative ileus and hospital stay.

Condition or disease	Intervention/treatment	Phase
Postoperative Ileus	Drug: Mosapride; Drug: Placebo	Phase 4

Detailed Description:

Methods. Design. Design A randomized controlled trial, triple blind with placebo. Study population Patients undergoing laparoscopic colorectal surgery. Italian Hospital of Buenos Aires. Argentina.

Inclusion and exclusion criteria

Participants will be eligible provided they are at least 18 years of age and under 85, are about to undergo colonic or upper rectum surgery with the diagnose of cancer o malignant polyp. People will be excluded if:

• They refuse to participate from the trial or the process of informed consent
• Have known allergies or hypersensitivity to Mosapride or lactose (used for placebo)
• Patients with ascites, hepatic metastases or carcinomatosis
• Patients who cannot receive Non-steroidal anti-inflammatory drugs
• Pregnancy or women at a fertile age who do not use double contraceptive agents
• Patients with conversion to laparotomy
• Patients with a Rectal tumor beneath 11 cm requiring low or ultralow rectal resection
• Patients with an stoma or who underwent simultaneous resection of other organs

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Effect of Mosapride on Postoperative Ileus in Patients Undergoing Colorectal Surgery
• Study Start Date: December 2015
• Estimated Primary Completion Date: December 2016
• Estimated Study Completion Date: December 2017

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo arm: intake of placebo (Lactose). 1 pill of the same characteristics as Mosapride every 8 hs with 30 ml tap water. This will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.	Drug: Placebo; 1 pill of the same characteristics as Mosapride every 8 hs with 30 ml tap water. This will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.; Other Name: Lactose
Active Comparator: Mosapride; Mosapride arm: intake of active drug (Mosapride). 15 mg per day divided into 3 oral intakes of 5 mg each (1 pill of Mosapride every 8 hs with 30 ml tap water). This treatment will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.	Drug: Mosapride; 15 mg per day divided into 3 oral intakes of 5 mg each (1 pill of Mosapride every 8 hs with 30 ml tap water). This treatment will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.; Other Name: Mosar

Outcome Measures

Primary Outcome Measures :

1. Number of days after Surgery until the recovery of bowel movement [ Time Frame: 1 to 5 days after surgery ]
   Effect of the administration of mosapride on the immediate postoperative on the recovery of bowel movements.

Secondary Outcome Measures :

1. Number of patients to develop adverse reactions to Mosapride [ Time Frame: 1 to 5 days after surgery ]
   To evaluate the safety of the administration of Mosapride after colorectal laparoscopic surgery.

Other Outcome Measures:

1. Number of days of Hospital stay after surgery. [ Time Frame: 18 months (end of protocol) ]
   To assess the effect of Mosapride on the reduction of Hospital stay days

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 18 to 85 years old
• Underwent colonic or upper rectum laparoscopic surgery with diagnose of cancer or malignant polyp
• Were operated on Italian Hospital of Buenos Aires

Exclusion Criteria:

• They refuse to participate from the trial or the process of informed consent
• Have known allergies or hypersensitivity to Mosapride or lactose (used for placebo)
• Patients with ascites, hepatic metastases or carcinomatosis
• Patients who cannot receive Non-steroidal anti-inflammatory drugs
• Pregnancy or women at a fertile age who do not use double contraceptive agents
• Patients with conversion to laparotomy
• Patients with a Rectal tumor beneath 11 cm requiring low or ultralow rectal resection
• Patients with an derivative stoma or who underwent simultaneous resection of other organs

Contacts and Locations

Contacts

Contact: Virginia M Cano Busnelli, MD; 54 11 66128852; virginia.cano@hospitalitaliano.org.ar

Contact: Natalia L Gomez, MD; 54 11 68364732; natalia.gomez@hospitalitaliano.org.ar

Locations

Argentina

Italian Hospital of Buenos Aires; Recruiting

Buenos Aires, State Capital, Argentina, 1199

Principal Investigator: Virginia M Cano Busnelli, MD

Sub-Investigator: Natalia L Gomez, MD

Sub-Investigator: Jeremias Goransky Patiño, MD

Sponsors and Collaborators

Hospital Italiano de Buenos Aires

Investigators

• Study Director: Carlos A Vaccaro, MD; Hospital Italiano de Buenos Aires

More Information

Publications:

Toyomasu Y, Mochiki E, Morita H, Ogawa A, Yanai M, Ohno T, Fujii T, Tsutsumi S, Asao T, Kuwano H. Mosapride citrate improves postoperative ileus of patients with colectomy. J Gastrointest Surg. 2011 Aug;15(8):1361-7. doi: 10.1007/s11605-011-1567-x. Epub 2011 May 24.

Narita K, Tsunoda A, Takenaka K, Watanabe M, Nakao K, Kusano M. Effect of mosapride on recovery of intestinal motility after hand-assisted laparoscopic colectomy for carcinoma. Dis Colon Rectum. 2008 Nov;51(11):1692-5. doi: 10.1007/s10350-008-9407-0. Epub 2008 Jun 27.

Seta ML, Kale-Pradhan PB. Efficacy of metoclopramide in postoperative ileus after exploratory laparotomy. Pharmacotherapy. 2001 Oct;21(10):1181-6.

Davidson ED, Hersh T, Brinner RA, Barnett SM, Boyle LP. The effects of metoclopramide on postoperative ileus. A randomized double-blind study. Ann Surg. 1979 Jul;190(1):27-30.

Furness JB, Costa M. Adynamic ileus, its pathogenesis and treatment. Med Biol. 1974 Apr;52(2):82-9. Review.

Jepsen S, Klaerke A, Nielsen PH, Simonsen O. Negative effect of Metoclopramide in postoperative adynamic ileus. A prospective, randomized, double blind study. Br J Surg. 1986 Apr;73(4):290-1.

Tollesson PO, Cassuto J, Rimbäck G, Faxén A, Bergman L, Mattsson E. Treatment of postoperative paralytic ileus with cisapride. Scand J Gastroenterol. 1991 May;26(5):477-82.

Brown TA, McDonald J, Williard W. A prospective, randomized, double-blinded, placebo-controlled trial of cisapride after colorectal surgery. Am J Surg. 1999 May;177(5):399-401.

• Responsible Party: Diego Hernan Giunta, MD, Principal Investigator, Hospital Italiano de Buenos Aires
• ClinicalTrials.gov Identifier: NCT02056405
• Other Study ID Numbers: 2104
• First Posted: February 6, 2014
• Last Update Posted: December 17, 2015
• Last Verified: December 2015

Keywords provided by Diego Hernan Giunta, MD, Hospital Italiano de Buenos Aires:

Postoperative Ileus; Mosapride; Colorectal laparoscopic surgery; Prolonged postoperative ileus

Additional relevant MeSH terms:

Ileus; Intestinal Obstruction; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Mosapride; Gastrointestinal Agents; Serotonin Receptor Agonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs